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Parkinson's Disease: Health-Related Quality of Life, Economic Cost, and Implications of Early Treatment
Jack J. Chen, PharmD
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Parkinson's Disease: Health-Related Quality of Life, Economic Cost, and Implications of Early Treatment

Jack J. Chen, PharmD

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder, marked by progressive increases in movement-related disability, impaired balance, and nonmotor symptoms. Its prevalence in the United States is expected to double within the next 20 years as the percentage of the elderly in the population grows. Patients with PD have twice the direct medical costs of those without PD, the majority of which occur later in the disease as disability and therapy-related complications increase. Greater awareness of a prodromal/premotor stage of the disease, efforts toward early and accurate diagnosis, and the continuous refinement of treatment paradigms provide an opportunity for discussion on the use of potential disease-modifying agents to slow or halt the progression of motor and nonmotor disability. Such compounds could not only significantly improve patient and caregiver quality of life, but substantially reduce direct and indirect costs. To date, numerous compounds have been evaluated in clinical trials, including coenzyme Q10, creatine, levodopa, pramipexole, rasagiline, ropinirole, and selegiline. None has demonstrated irrefutable and enduring disease-modifying qualities, although the best available clinical evidence appears most promising for rasagiline.

(Am J Manag Care. 2010;16:S87-S93)

 

Introduction

Parkinson's disease (PD) is the second most common neurodegenerative disorder, marked by increasing movement-related disability, including tremor and bradykinesia, impaired balance and coordination, and cognitive changes.1 It affects up to 1 million people in the United States and up to 5 million worldwide.1 The prevalence of PD increases with age, with approximately 1% of those aged 60 years or older affected, 4% or more of those aged 80 years or older,2 and approximately 5.2% of those in nursing homes.34 Given the growing elderly population in the United States, the number of individuals with PD is expected to double by 2030.

 

Such an increase will place a significant burden on healthcare systems and caregivers given the progressive nature of PD, associated disability, and significant caregiving required in the later stages of the disease. With the expected increase in PD prevalence, it can be anticipated that the disease will continue to exact a significant direct and indirect economic cost. Thoughtful consideration into treatment decisions can result in more optimal healthcare utilization without sacrificing health-related quality of life (HRQOL) and economic costs.

 

Economic Costs of PD and Impact on Health-Related Quality of Life

Overall, the annual economic impact of PD in the United States is estimated at $10.8 billion, 58% of which is related to direct medical costs.5 Annual direct medical costs per patient with PD are estimated to be between $10,043 and $12,491, more than double that of patients without the disease.5,6 Prescription drugs account for approximately 14% to 22% of costs, with nursing home care the largest component at approximately 41%. Annual indirect costs, including lost workdays for patients and caregivers, are estimated at $9135.5

 

As important as economic costs are to any discussion of PD-related resource utilization, it is also critical that payers and providers consider the significant impact the disease has on HRQOL. HR QOL assesses an individual's perceived effect of the illness on their physical, psychological, and social daily lives.7 It is important in determining the effectiveness of therapies for PD at both the individual and population levels.8 For managed care providers, it presents an important parameter to measure the effectiveness of management strategies and quality of care.7 HRQOL measures are also important in assessing the value of drug therapy, particularly for chronic conditions such as PD, and in determining the appropriate placement of medications on plan formularies.9,10





As would be expected for any chronic and progressively worsening disorder, PD has a significant impact on the HRQOL for both patients and their caregivers.11 In a large Veterans Administration cohort, patients with PD exhibited lower scores on the physical and mental health dimensions of HRQOL compared with patients with 8 other neurologic or chronic conditions, including diabetes, congestive heart failure, angina/coronary heart disease, and stroke.12 Of note, nonmotor disability, particularly depression, insomnia, and other mental health factors, appear to have a greater negative effect on HRQOL than motor deficits.8,13-15





Etiology and Clinical Course of PD

Aging, in addition to multiple other factors, appears to contribute to the pathoetiology of PD. Approximately 5% to 10% of patients demonstrate a familial pattern of the disease, some of which are associated with linkages to a dozen different gene mutations.16 Environmental factors likely interact with genetic factors to increase the risk of PD, including herbicide or pesticide exposure.17-20 Interestingly, epidemiologic studies have consistently associated an inverse correlation between cigarette smoking and coffee consumption for the lifetime development of PD.21





The brains of individuals with PD are marked by degeneration and loss of dopaminergic neurons in the substantia nigra.1 Nondopaminergic pathways are also involved, including cholinergic and norepinephrine neurons in the basal forebrain, serotonin neurons in the midbrain raphe, and other neurons in the brain stem, spinal cord, and peripheral autonomic nervous system. Pathology in many of these neuronal systems likely contributes to the nonmotor manifestations of the disease.16,22





More recently, it has been postulated that PD may be a prion disorder given the prion-like behavior of alphasynuclein protein aggregates. These aggregates comprise a significant portion of the Lewy bodies that are a cellular hallmark of PD.23





The clinical course of PD often begins with nonmotor symptoms such as constipation, hyposmia (reduced sense of smell), and rapid eye movement (REM) sleep behavior disorder (RBD). Patients are usually not diagnosed, however, until they exhibit obvious motor symptoms, consisting of resting tremor, rigidity, and/or slowness of movement (bradykinesia).1,24,25 About one third of patients do not develop a resting tremor, and this has been reported to be prognostic of a more rapidly progressive disease course.26 As the disease progresses, patients exhibit disability due to bradykinesia, rigidity, gait and balance difficulty, and falls.24 Additionally, dopaminergic-related side effects from medications become more problematic. In more advanced stages of the disease, disabling cognitive symptoms, such as dementia, are more common.24





Several assessment and rating scales provide clinically important information on changes in PD severity and disability. These include the Unified Parkinson's Disease Rating Scale (UPDRS), which is undergoing revision to better account for nonmotor symptoms, Webster's Columbia University Rating Scale (CURS), Northwestern University Disability Scale (NUDS), and the Hoehn and Yahr scale.27 A recent analysis correlated disability with the UPDRS and identified specific motor and total scores to assist clinicians in determining clinically meaningful changes in PD progression and response to therapy.28





Implications of Prodomal/Premotor Stage

PD is comprised of motor and nonmotor signs and symptoms. It is recognized that extranigral neuropathologic changes precede the degeneration of nigrostriatal dopaminergic neurons; thus, nonmotor features antedate the onset of motor features. However, diagnostic criteria for PD are validated based on motor features. Premotor clinical features include autonomic dysfunction (impaired olfaction, cardiac sympathetic denervation, urinary disturbances), gastrointestinal disturbances (constipation), neuropsychiatric disorders (depression, mild cognitive impairment, RBD), and sensory disorders (pain, restless legs syndrome). Such symptoms may occur up to 10 years prior to motor symptoms and diagnosis.29-32 The Table describes nonmotor symptoms that may be present in the premotor stage of PD.





There are several stages related to neuronal changes, with earlier stages occurring in areas other than the substantia nigra. As Braak and his coauthors noted: "Were it to become possible to diagnose PD in the presymptomatic stages 1 or 2, and were a causal therapy to become available, the subsequent neuronal loss in the substantia nigra could be entirely prevented."32,33 By the time patients are diagnosed, however, substantial neuronal damage has already occurred in the substantia nigra, with dopamine levels at least 30% to 40% lower than normal.16,34





Greater awareness and recognition of the presence of premotor symptoms of PD have raised the possibility of very early diagnosis (before appearance of motor features). Imaging studies utilizing dopamine transporter tracers and nigral ultrasound methods demonstrate the potential for use in earlier diagnosis.34 Given increased knowledge of the premotor phenotype of PD, a battery of tests including assessment of nonmotor features, olfactory testing, cardiac scintigraphy, and neuroimaging may one day provide a means of reliably diagnosing PD at an early stage of the disease. Ideally, then, disease-modifying (neuroprotective) therapies designed to slow or halt disease progression would be initiated. Although disease-modifying therapies may provide a benefit in moderate-to-advanced PD, initiation of therapy in early disease would provide greater benefit.





 
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